We propose to study risk factors for multiple primary anogenital cancers and to continue our case-control studiers of cervical and vulvar cancer. Both studies have as their goal the elucidation of factors, beyond HPV, that contribute to the etiology of anogenital cancer. The new, major focus of this proposal will be risk factors for the development of multiple primary anogenital tumors. We will match each of these women to a women with one anogenital tumor who does not go on to develop a second tumor. We will interview multiple primary anogenital cancer cases and matched single primary controls about characteristics that may be related to their risk of a second primary tumor, and collect archival tumor tissue to test for HPV DNA types and non- prototype variants. Blood will be collected for serologic and genetic testing. We plan to determine whether the risk of multiple primary anogenital cancers is related to: 1) cigarette smoking, particularly continued smoking following the initial primary; 2) HLA class II alleles; 3) family history of anogenital cancers; 4) HPV type and non-prototype variant in the initial primary cancer. The data from this study may contribute to the design of clinical monitoring for anogenital cancer patients at high risk of second primary cancer, and may provide targets for behavior modification that could reduce the incidence of multiple anogenital tumors. In continuing our case-control study, we will example HPV co-factors in relation to risk cervical and vulvar carcinoma. The study will be conducted in three counties of western Washington. All women engaged 18-74 who are diagnosed from January 2000 through December 2004 with cervical or vulvar cancer will be identified through the population- based Cancer Surveillance System. Cases and population-based controls will be interviewed regarding history of sexually transmitted diseases, smoking status, family history of anogenital and other cancers, as well as known risk factors for each tumor. Tissue specimens will be obtained from all cases and will be assayed for HPV DNA. Blood will be collected and tested for antibodies to HPV and for HLA alleles. The data will provide sufficient power for testing important interactions among HLA alleles, and between HLA alleles and lifestyle risk factors.